ADVANCE/Lilly presents pivotal clinical trial data for raloxifene, a selective estrogen compound.

(ADVANCE) WASHINGTON--(BW HealthWire)--June 5, 1997--Data presented today by Eli Lilly and Company suggest that a novel compound currently under study for the prevention of osteoporosis may offer a new choice of therapy for preserving the health of postmenopausal women. These clinical trial data were presented at the Fourth International Symposium on Osteoporosis Research Advances and Clinical Applications sponsored by the National Osteoporosis Foundation (NOF).

The compound, raloxifene, is among the first in a new class of drugs called selective estrogen receptor modulators (SERMs), which may present an alternative to hormone replacement therapy in the prevention of postmenopausal health risks, including osteoporosis. SERMs are being studied for their selective ability to act like estrogen in the skeleton and the cardiovascular system, while blocking estrogen's effects in the breast and uterus.

There are 150 million postmenopausal women in the world today, with 37 million postmenopausal women living in the United States. As a woman makes the natural transition through menopause and her ovaries stop producing estrogen, she may face an increasing number of long-term health risks, such as osteoporosis and cardiovascular disease, in addition to the natural symptoms of menopause. While estrogen replacement therapy may alleviate these symptoms and give long-term protection, some women complain of side effects, including continuation of monthly bleeding, breast tenderness and breast pain, and some fear an increased risk of breast and/or uterine cancers.

Raloxifene Phase III clinical trial results

Raloxifene prevented bone loss in the spine and hip compared with calcium-supplemented placebo in Phase III clinical trials. The compound increased bone mineral density, an indicator of risk for fracture, by 2 to 3 percent compared with placebo at all skeletal sites measured (hip, spine and total body). The increases in bone mineral density, which amounted to 1 to 2 percent above baseline values, were statistically significant at 12 months and remained so at 24 months. In contrast, the calcium-supplemented placebo group continued to lose bone mineral density throughout the 24 month period. The effects of raloxifene on preventing skeletal fractures are still under investigation.

"A woman may lose as much as 20 percent of her bone mass in the first five years following menopause," according to Ethel Siris, M.D., Director of the Osteoporosis Center, Columbia University. "Preserving this bone mass is critical to maintaining a woman's long-term health and vitality after menopause by decreasing her risk of disabling fractures as she ages."

Raloxifene's effects on other organs were also evaluated in Phase III clinical trials in order to understand the compound's impact on the long-term health of postmenopausal women in comparison to other therapies.

The effects of raloxifene on lipids and other potential indicators of risk for heart attacks and strokes were evaluated throughout the trials and specifically in a 6-month study of 390 postmenopausal women. Raloxifene produced a statistically significant reduction in LDL and total cholesterol, which when increased are associated with greater risk for hardening of the arteries and heart attacks. However, raloxifene did not change HDL cholesterol or triglycerides. Raloxifene also produced a statistically significant reduction in serum fibrinogen, the elevation of which has been suggested to be an additional risk factor for heart disease. These results are comparable to those in numerous studies of estrogen use after menopause, which may indicate a reduced risk of cardiovascular disease. Based on these Phase III findings, additional long-term research on raloxifene's effect on the heart are being considered.

In the uterus, raloxifene did not stimulate the tissue, nor did it induce spotting or bleeding. In clinical trials, endometrial thickness was evaluated every 6 months for two years. There were no differences between the raloxifene and placebo groups with respect to adverse tissue effects or uterine bleeding. In contrast, hormone replacement therapy stimulated the endometrium and caused unwanted symptoms of spotting and bleeding in patients who participated in clinical trials.

Raloxifene did not stimulate breast tissue in women in clinical trials. Raloxifene was not different from placebo with regard to breast swelling, tenderness or pain, which may occur in women undergoing hormone replacement therapy. In addition, raloxifene was not associated with an increased risk for breast cancer. In light of these encouraging results, the company continues to evaluate raloxifene's effects in the breast in ongoing clinical trials.

The most commonly observed side effect in clinical trials of raloxifene was hot flashes. Patients taking raloxifene reported a slightly higher rate of hot flashes (24 percent) than did patients taking placebo (18 percent). The onset, severity and duration of these hot flashes were comparable to placebo. In addition, discontinuation rates due to hot flashes were less than 2 percent in both groups.

Raloxifene is currently being studied in more than 12,000 women in more than 25 countries.

The NOF is the nation's leading authority on the diagnosis, prevention and treatment of osteoporosis. Established in 1986 as America's only nonprofit voluntary health organization dedicated to reducing the widespread prevalence of osteoporosis, the NOF has developed programs, policies and strategies designed to comprehensively address this major public health problem.

Eli Lilly and Company is a global research-based pharmaceutical corporation headquartered in Indianapolis, Indiana, dedicated to creating and delivering superior health care solutions -- by combining pharmaceutical innovation, existing pharmaceutical technology, disease prevention and management and information technologies -- in order to provide customers worldwide with optimal clinical and economic outcomes.

(End of advance for release 5 p.m. EST June 5.)

CONTACT: Eli Lilly and Company, Indianapolis

Elisabeth Ritz, 317/277-1172

Danielle Halstrom, 317/277-6990